Crystallizers process for

Solidification. Production of a product in a form suitable for use and acceptable to the consumer also may be an objective of a crystallization process. For example, the appearance of sucrose (sugar) varies with local customs, and deviations from that custom could lead to an unacceptable product. A final crystallization may thus be called for to bring the product appearance into compliance with expectations. 

The optimal network increases total residence time by 48 per cent when compared with an equivalent MSMPR of the same volume and throughput. This increase would translate into a similar increase in mean crystal size and a 78 per cent increase in yield. Exactly the same residence time as for the single crystallizer have been reported from simple cascade configurations previously designed for stage-wise crystallization processes for slight improvements in... 

Many dry solid parenteral products, such as the cephalosporins, are prepared by sterile crystallization techniques. Control of the crystallization process to obtain a consistent and uniform crystal form, habit, density, and size distribution is particularly critical for drug substances to be utilized in sterile suspensions. For example, when the crystallization process for sterile ceftazidime pentahydrate was modified to increase the density and reduce the volume of the fill dose, the rate of dissolution increased significantly. 

The design of crystallization processes for the manufacture of Active Pharmaceutical Ingredients is a significant technical challenge to Process Research and Development groups throughout the Pharmaceutical and related industries. It requires an understanding of both the thermodynamic and kinetic aspects of crystallization, to ensure that the physical properties of the product will consistently meet specification. Failure to address these issues may lead to production problems associated with crystal size, shape and solubility, and to dissolution and bioavailability effects in the formulated product. 

All of our observations lead us to believe that the crystallization of VPI-5 involves a solid phase reordering process. This solid phase transformation does not involve TBA as either a template or a space-filler. TBA may be present in the solid phase in very low concentrations that are below detection limits by IR and NMR and may still play some role in the crystallization mechanism. Also, it may serve to moderate the pH of the reaction mixture during its formulation and heating such that certain aluminophosphate precursor species are present in the solid phase. Here we will explore these two possibilities in order to further understand the crystallization process for forming VPI-5. 

The interaction between solvents is important. For example, the development of a successful crystallization process for purification and isolation of an organic compound requires the selection of a suitable solvent or solvent mixture to date, no logical method has been estabhshed for determining the best solvent combination. The process chemist or engineer often employs a trial-and-error procedure to identify an appropriate solvent system, the success of which is dependent on experience and intuition. One approach utilizes a group-contribution method (UNIFAC) to predict a... 

The crystallization process for concentrating bismuth in lead by squeezing the eutectic (high in bismuth) liquid out of the solidified high lead portion at a temperature within the melting range of the alloy is seldom used. 

This study showed that the overall crystallization processes for mor-denite, zeolite X, and zeolite A were similar. However, the physical properties of the crystallizing system determine the rate-limiting step for a particular zeolite synthesis. In the case of mordenite in which both the viscosity of the batch composition and the morphology of seed crystals were varied, it was observed that diffusion in the liquid phase was the ratedetermining step. For zeolite X the actual growth rate on the crystal-liquid interface was the rate-limiting factor as shown by identical conversion rates for the seeded and unseeded systems. For zeolite A in the system chosen, both processes influenced the conversion rate. 

Salt screening is often conducted in parallel to the polymorph screening in case a scalable crystallization process for the drug is not found. Chapter 11 in this book is devoted to this topic, and the reader is directed there for a detailed discussion. 

Fig. 10.35. Two-stage crystallization process for recovery of high-purity para-xylene from mixed xylenes. (Reproduced from Hydrocarbon Processing, p. 175, Nov. 1985. Copyright 1985 by Gulf Publishing Co.)...

Although the crystallization process for strategies 1-4 inherently affords homochiral single crystals, only the use of homochiral tectons guarantees that all crystals will be of the same enantiomorph. Indeed, batches of crystals will often be heterochiral as both enantiomers tend to be formed equally during crystallization. Fortunately, it has been demonstrated58 that formation of homochiral bulk materials can be afforded by seeding with the desired enantiomer. 

Sensors for particle size characterization used for crystallization include ultrasound attenuation measurement/ " laser diffraction/ and laser backscatteiing/ commercially called focused beam reflectance measurement (FBRM). Ultrasonic attenuation spectroscopy has been used to monitor the crystallization process parameters such as the crystal size distribution, concentration, and the onset of nucleation during batch crystallization of L-glutamic acid/ Off-line laser diffraction has been used to measure the crystal size distribution in the development of the crystallization process for a pharmaceutical intermediate/ ... 

Synthetic zeolites are used in a variety of catalyst and adsorbent applications. Most zeolites are synthesized in batch processes, but U.S. 6,773,694 (to UOP) describes a continuous crystallization process for zeolite formation. The resulting crystals can be dried and formulated into catalysts, adsorbents, and other products. Estimate the costs of producing zeolite X and Mordenite by this method. 

In the presence of polymorphs, developing a proper crystaUization process to control the desired crystal form is a real challenge. A good understanding of solid-liquid equilibrium behaviors under different conditions—for example, the temperature or solvent mixmre— is a must. Seeding and control of supersaUiration are two critical, if not indispensable, requirements. Example 7-5 shows an example of developing a crystallization process for a polymorphic compound. 

At the end of this chapter, a brief set of proposed steps is given for the development of a new crystallization process for a pharmaceutical compound. 

Decamp WH. Regulatory considerations in crystallization processes for bulk pharmaceutical chemicals a reviews perspective. In Myerson et al., eds. Proceedings of the 1995 Conference on Crystal Growth Org Mater. Washington DC American Chemical Society, 1996 65-71. 

A U.S. Food and Drug Administration (FDA) reviewer s perspective of regulatory considerations in crystallization processes for bulk pharmaceutical chemicals has been presented by DeCamp (1996). In this paper, he stated that... 

Crystallization Processes for Active Pharmaceutical Ingredients —From Art to Science... 

In Equation 18.4, it is shown that filtrate flow rate strongly depends on particle size, which additionally influences the porosity of the filter cake. One can readily conclnde that controlling both the particle size and PSD and avoiding the formation of fines (which may be triggered by unwanted nncleation events in an indnstrial crystallization process, for example) are vitally important. 

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